Helminthic infections are major public health concerns in both tropical and temperate areas of the world. Exciting new evidence suggests that genetic factors may play important roles in determining susceptibility to infection for a number of these diseases. This project proposes a genomic scan to detect and localize the specific genes that influence susceptibility to infection with hookworm, roundworm, and whipworm in 1205 individuals belonging to the single largest pedigree of the Jirel population of eastern Nepal. Building upon 14 years of genetic research with the Jirel population, including three years of research on the genetic epidemiology of intestinal worm infections, this project will utilize the outstanding existing database and resource of helminthic infection data, blood samples, and pedigree information, to perform the first large-scale genomic scan for genes influencing susceptibility to these important diseases. We will use automated genotyping techniques to place STR markers every lOcM across the genome. We will then use state-of-the-art linkage analysis methods to detect genes influencing quantitative phenotypes associated with helminthic infection including initial egg counts and worm counts determined from stool samples collected for 96 hours following treatment with albendazole for hookworm, roundworm and whipworm. These helminthic infection phenotypes were determined at two points in time, in an initial survey and in a follow-up sample from 1 year after the initial survey. This project will provide new information about the genetic determinants Of susceptibility to intestinal worm infections.